Reduced disease severity following therapeutic treatment with angiotensin 1-7 in a mouse model of multiple sclerosis
AffiliationUniv Arizona Hlth Sci, Ctr Innovat Brain Sci, Coll Med, Dept Pharmacol
KeywordsExperimental autoimmune encephalomyelitis
MetadataShow full item record
PublisherACADEMIC PRESS INC ELSEVIER SCIENCE
CitationLund, B. T., Stone, R., Levy, A. M., Lee, S., Amundson, E., Kashani, N., ... & Kelland, E. E. (2019). Reduced disease severity following therapeutic treatment with angiotensin 1–7 in a mouse model of multiple sclerosis. Neurobiology of disease, 127, 87-100.
JournalNEUROBIOLOGY OF DISEASE
Rights© 2019 Elsevier Inc. All rights reserved.
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AbstractMultiple Sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by autoimmune and neurodegenerative pathologies for which there is no cure and no defined etiology. Although several, modestly effective, disease modifying drugs are available to treat MS, there are presently no treatments that offer neuroprotection and prevent clinical progression. Therapies are needed that control immune homeostasis, prevent disease progression, and stimulate regeneration in the CNS. Components of the renin-angiotensin-system (RAS) have recently been identified as chemical mediators in the CNS and in neurological disease. Here we show the beneficial effect of therapeutic treatment with the Mas receptor agonist and metabolite of the protective arm of RAS, angiotensin 1-7 (A(1-7)), in the experimental autoimmune encephalomyelitis (EAE) animal model of MS. Therapeutic treatment with A(1-7) caused a dose-dependent reduction both in clinical disease severity and progression, and was dependent on Mas receptor activation. Further analysis of the most optimal dose of A(1-7) treatment revealed that the reductions in clinical disease course were associated with decreased immune infiltration and demyelination, axonal loss and oxidative stress in the spinal cord. In addition A(1-7) treatment was also associated with increases in circulating alternatively activated monocytes/macrophages.
Note12 month embargo; available online 25 February 2019.
VersionFinal accepted manuscript
SponsorsDepartment of Defense, USC Clinical and Translational Science Institute, National Multiple Sclerosis Society